High incidence of cardiovascular events in Rheumatoid Arthritis cohort not explained by traditional risk factors
Patients with rheumatoid arthritis (RA) have a shortened lifespan compared to age- and gender-matched controls. Recent studies suggest that this is largely due to increased mortality from premature cardiovascular disease. It is unclear, however, whether enhanced rates of cardiovascular deaths result from a higher prevalanece of traditional cardiovascular risk factors, or due to the inflammatory rheumatoid process itself. Del Rincon et al (Arthritis Rheum 44:2737-2745, 2001) compared the incidence of cardiovascular (CV) events in 236 consecutive patients with RA to the incidence in an epidemiological cohort (SAHS cohort) participating in a study of atherosclerosis and CV disease. The investigators calculated the age- and sex-stratified incidence rate ratio (IRR) of CV events between the 2 cohorts and used Poisson regression to adjust for age, sex, smoking status, diabetes mellitus, hypercholesterolemia, systolic blood pressure, and body mass index. Only RA patients aged 20-65 were included in the Poisson regression (since this was the targeted age range of the SAHS cohort.)
Results: 15 CV events occurred in 236 RA patients in a total observation period of 252 patient-years. Seven of these incident events occurred in RA patients aged 20-65, for an incidence of 3.43 per 100 patient-years. For the SAHS cohort, 4,635 persons were followed for 33,881 person-years, during which 200 new CV events occurred, for an incidence of 0.59 per 100 person-years. The age- and sex-adjusted IRR of incident CV events associated with RA was 3.96 [95% confidence interval, 1.86-8.43]. After adjusting for CV risk factors using Poisson regression, the IRR was 3.17 [95% confidence interval, 1.33-6.36].
Conclusions: RA patients had a significantly increased risk of incident CV events compared to non-RA controls. This increased risk could not be explained by traditional CV risk factors, suggesting that other mechanisms are operable. The authors suggest that physicians should be aware of the increased risk of CV events in RA patients and implement appropriate diagnostic and therapeutic measures.
Editorial Comment: This is a well designed study. One of its major strengths is the inclusion of a large control population that is demographically very similar to the RA population. Although the number of RA patients and associated CV events is quite small compared to the control population, there was nonetheless a highly significant 4-fold increase in risk for CV events in the RA patients. This finding is consistent with prior studies that only examined fatal CV events. Another major strength of this study is the systematic assessment of traditional CV risk factors and, contrary to some prior reports, these risk factors did not seem to be increased in RA patients compared to controls when stratified by age. In fact, consistent with several prior reports, RA patients were LESS likely to have hypercholesteremia than age- and sex-matched controls. Unfortunately, in this study, inflammatory markers (ESR, CRP), use of corticosteroids, homocysteine levels, and level of exercise were not factored into the model to assess their contributions to the risk for CV events. It has been speculated that the inflammatory process in RA plays a major role in the evolution of CV disease but few data to confirm or refute this are yet available.